This study proposes to characterize in the primate the relationship between pain and temperature primary afferents and spinothalamic neurons, and to study the roles which intraspinal and supraspinal neurons may play as modulators of these connections. Our objective is to provide a structural description of pain relay mechanisms which can be correlated with physiological and pharmacological events in pain sensation. Recently, the neuropeptides substance P and enkephalin, and an indoleamine, serotonin, have been shown to be important agents in the function of spinal cord circuits mediating pain. Substance P may be a transmitter of some nocieptive primary afferents, and enkephalin and serotonin appear to be associated with systems whichmay reduce pain sensation. The anatomical basis of the function of these substances is little known, particularly in primates and man. By applying immunohistochemical methods, alone and in combination with other anatomical and physiological techniques, precise identification of the elements of the spinal circuits involved in pain may bae possible. Previous studies in this laboratory have described the distribution of primary afferents in the primate spinal cord with light microscopy, and the distribution of opiate receptors and their relationships to primary afferents. Current studies are focused on the distribution of substance P, enkephalin, and serotonin in the primate spinal cord and brain stem using light and electron microscopy. We now propose to continue and expand these studies by quantitative analysis of the ultrastructural relationships of synaptic terminals containing these substances; applying a new method of EM serial sectioning which allows multiple labelling of terminals and specific analysis of the ultrastructural relationships of synaptic terminals containing these substances; using autoradiographic labelling of primary afferents or descending pathways combined with immunohistochemistry for EM analysis identified by physiological recording and retrograde fluorescent tracing to identify the origins of terminals containing these substances.